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Positive Results Announced From Resten-NG Phase 2 Trial

PORTLAND, Ore. — Nov. 10, 2004 — AVI BioPharma, Inc. (Nasdaq: AVII), today announced positive results from its AVAIL Phase II clinical trial, which investigated the effects of antisense drug Resten-NG® against cardiovascular restenosis. Resten-NG is a third-generation NeuGene® antisense drug targeting the key regulatory gene in restenosis. It is the most advanced antisense agent in development by AVI.

Nicholas Kipshidze, M.D., an interventional cardiologist from Lenox Hill Hospital in New York, presented the results at the American Heart Association’s annual meeting in New Orleans. The AVAIL multicenter clinical study enrolled coronary artery disease patients who had a high risk of restenosis following balloon angioplasty. Patients were randomized into three blinded study groups that included a control group and two treatment arms.

Using the Infiltrator catheter and two dose levels within the treatment arms, investigators delivered Resten-NG to the sites of balloon angioplasty. Resten-NG in the therapeutic dose arm demonstrated statistically significant efficacy in preventing restenosis determined by both quantitative angiography and intravascular ultrasound compared with the control arm and the sub-therapeutic dose arm. Further, Resten-NG significantly reduced the neointimal growth that contributes to the failure of angioplasty intervention. The binary restenosis rate of 33 percent in the control arm was reduced to approximately 8 percent, a 75 percent reduction of the restenosis rate, among patients who received a therapeutic dose.

"This study clearly demonstrates that the Resten-NG antisense agent really works," said Dr. Kipshidze. "With these well-documented results in high-risk patients, Resten-NG should now proceed to phase III clinical studies." Lenox Hill Hospital was one of the participating trial sites.

Resten-NG is a third-generation antisense agent that targets the key regulatory gene involved in cardiovascular restenosis, the transcription factor referred to as c-myc. It is believed to regulate the many downstream genes that produce the pathology of restenosis, namely cell migration and adhesion, collagen formation, secretion of extra-cellular matrix, and cell proliferation, among others. The c-myc gene is immediately activated by the injury to the vascular lining during angioplasty and stent placement and peaks at 24 to 48 hours before subsiding. NeuGene antisense drugs are particularly suited to prevent this process because they can be delivered immediately following injury to the angioplasty site by a variety of means including catheter and stent elution, or by systemic delivery using AVI’s microparticle delivery system, Resten-MP™.

"Efficacy from this Phase II clinical trial is an important milestone for AVI’s platform NeuGene technology," said Denis Burger, Ph.D., chief executive officer of AVI BioPharma. "AVI has plans for more advanced clinical trials with both its drug-eluting stent and systemic delivery platforms, which could lead to European and FDA approval if successful."

AVI intends to initiate Phase III clinical trials with its own drug-eluting stents in Europe, which will lead to CE Mark approval if clinically successful. To accomplish this, AVI has recruited a team of employees and consultants who have extensive experience with devices used in interventional cardiology and direct experience in clinical trials and the approval process in both Europe and America. There are four key components to this program: the stent, the balloon delivery system, the drug, and the coating material to bind and release the drug from the stent.

AVI has successfully assembled these four components into a cohesive system that it believes will be the next generation of drug-eluting stent, or DES. The most important component in the system is the drug, and Resten-NG has advantageous characteristics when compared with the drug component in the Cypher or Taxus drug-eluting stents. The coating that AVI is qualifying is the one used by Johnson & Johnson on its FDA-approved Cypher DES. Using this coating, AVI has been able to exceed both the loading and elution characteristics required for Resten-NG. With the experience and expertise of new staff members, AVI has developed its own stent to match with Resten-NG and this coating technology. The final component is the balloon delivery system that is now finishing qualification with the sterilization techniques suited for use with Resten-NG.

Investigators and European clinical sites have been identified for a European Phase III clinical trial. The anticipated study timeline will be detailed at the initiation of the trial. AVI also expects to offer its DES package for out-licensing and development in the United States following the initiation of the trial.

AVI continues to make progress on its program with Resten-MP. Resten-MP is Resten-NG delivered via intravenous injection using AVI’s patented microparticle delivery technology. In preclinical studies, this was as effective as Resten-NG delivered by catheters or stents in preventing cardiovascular restenosis and demonstrated many advantages. AVI plans to initiate additional Phase II clinical studies with Resten-MP at additional sites in combination with the Taxus DES and with bare metal stents later this year and in early 2005 to complement its ongoing program.

Source: AVI Biopharma

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